Biochip microarrays can be two-dimensional arrays of reference biological materials on substrates such as glass membranes or similar materials. Microarrays are fabricated by printing small volumes of solution containing the reference biological material on a substrate. Types of technologies for fabricating biochip microarrays include photolithography, contact printing with split pins, and non-contact dispensing.
When photolithography using optical masks is used, the microarrays are sometimes referred to as “chips” because the photolithographs techniques use are similar to those used in semiconductor manufacturing. Typically more than 100,000 different samples can be created on a 1.3 cm×1.3 cm substrate surface, but the technique is expensive and limited to oligonucleotide probes of twenty to thirty base sequences because the oligonucleotide probes are usually synthesized in situ on the substrate from nucleotides in solution.
Split pin contact printing is very simple and easily implemented. Volumes of reference biological materials are held within the gap of a pin with a split end by capillary action, until transferred to the substrate by contact. Split pin contact printing is one of the most popular current technologies for fabricating microarrays, however the sample volume printed for each spot depends on the physical dimensions of the split end of the pin which are difficult to control. Consequently the accuracy and reproducibility of printed sample fluid volumes are difficult to control at the nanoliter to microliter quantities typically dispensed.
Non contact dispensing techniques, in some ways similar to technology used in ink jet printers, can provide fluid delivery in highly accurate and repeatable volumes in nanoliter and microliter volumes. Furthermore, because contact between the dispenser and the substrate is not required for capillary fluid flow, as for the case of the split pin technique, printing speeds can be much faster, often up to 100 dots per second, or more. Non contact dispensing techniques include piezoelectric jet, thermal bubble jet, and microvalve control. Piezoelectric jet and thermal bubble jet sample fluid applicators, derived from inkjet printer technologies, have been adapted to biochip microarray manufacture, however equipment costs tend to be high. The microvalve dispensing technique tends to require lower equipment costs because it principally comprises a pump or similar component, a microvalve (generally solenoid operated), tubing that connects the pump and the microvalve, a nozzle, and associated tubing and connectors. The microvalve is generally proximate to the nozzle and can accurately and reproducibly control the amount of previously aspirated sample fluid that is dispensed, through the precise control of the time that the microvalve is open and the magnitude of the pressure applied on the fluid in the tubing.
The BioJet Plus™ series dispensers from the United States Company, Biodot, Inc. in Irvine Calif., are examples of dispensers based on microvalve non-contact dispensing technology. A syringe pump is used aspirate sample fluid to fill nearly all of the operative volume of the apparatus (including the syringe pump) with the sample fluid, prior to dispensation. Aspirate recovery upon dispensation is typically fifty to ninety percent, depending on process parameters and sample fluid properties, because of residual sample fluid retained by the system. Such wastage of biological sample fluid can be very costly. Also, the BioJet Plus™ series dispensers can take a long time to purge residual sample fluid when changing samples because it is difficult to expel all residual droplets and bubbles using the syringe pump before aspirating a new sample.
The SmartArrayer from Beijing Capitalbio Corporation (China Patent Application No. 200,420,093,039.4) similarly uses a pressure tuning module to aspirate and expel sample fluid, but most of the operative volume of the apparatus (including the tubing connecting the pressure tuning module and the microvalve) can be partly filled with air, in order to reduce sample wastage.